Astragaloside IV, a new cycloartane-type triterpene glycoside extract of Astragalus membranaceus Bunge, has been identified for its potent immunoregulatory, antiinflammatory, and antifibrotic actions. Here we investigated whether astragaloside IV could suppress the progression of airway inflammation, airway hyperresponsiveness, and airway remodeling in a murine model of chronic asthma. BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks. Astragaloside IV was orally administered at a dose of 50 mg·kg-1·day-1 during each OVA challenge. Astragaloside IV treatment resulted in significant reduction of eosinophilic airway inflammation, airway hyperresponsiveness, interleukin (IL)-4 and IL-13 levels in bronchoalveolar lavage fluid, and total immunoglobulin E levels in serum. Furthermore, astragaloside IV treatment markedly inhibited airway remodeling, including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. In addition, the expression of transforming growth factor-β1 in the lung was also reduced by astragaloside IV. These data indicate that astragaloside IV may mitigate the development of characteristic features in chronic experimental asthma.

AbstractAstragaloside IV is the major active constituent of Astragalus membranaceus, which has been widely used for the treatment of cardiovascular diseases in China. However, the effects of astragaloside IV on myocardial ischemia and its mechanisms of action remain largely unknown. In this study, we have examined the effects of astragaloside IV on myocardial infarction and coronary flow in vivo and in vitro. The possible roles of its antioxidative and nitric oxide-inducing properties were also explored. Astragaloside IV significantly reduced infarct size in dogs subjected to coronary ligation in vivo. Astragaloside IV also improved post-ischemic heart function and ameliorated reperfusion arrhythmias in rat hearts in vitro. The cardioprotection of astragaloside IV was accompanied by a significant increase in coronary flow both in vivo and in vitro. The nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester partially abrogated astragaloside IV's protective effect on heart function. Myocardial antioxidative enzyme superoxide dismutase activity increased with astragaloside IV administration. These data suggest the potential roles of antioxidative and nitric oxide-inducing properties of astragaloside IV in its protection from myocardial ischemia.

Association of attenuating left ventricular remodeling in murine dilated cardiomyopathy with phosphorylation of p38MAPK after interference by astragalosideSHEN E,CHEN Rui-zhen,YANG Ying-zhen,GUO Qi,YU Yong,ZOU Yun-zeng,CHEN Hao-zhu(Key Laboratory of Viral Heart Diseases,Ministry of Public Health,Shanghai Institute of Cardiovascular Diseases,Zhongshan Hospital,Fudan University,Shanghai 200032,China.) AIM:To investigate the effects and mechanism of astragaloside(Astr)on ventricular remodeling in CVB3-induced murine dilated cardiomyopathy(DCM).METHODS:BALB/c mice were inoculated ip repeatedly with CVB3 by increment to establish animal model of DCM(n=30).Other mice infected with CVB3 were fed with Astra(0.6 mg·kg-1·d-1)as DCM+Astr(n=20).Control mice(n=10)were treated with same volume of EMEM without CVB3.The diameter of LV and cardiac function were measured by high frequency echocardiography.Serum concentrations of PINP,PICP and PIIINP were detected by enzyme linked immunosorbent assay(ELISA).The collagen in myocardium was stained with Sirius red.collagen volume fraction(CVF)and collagen I were calculated by image analysis software.Expressions of collagen type I and III were confirmed by reversed transcriptional polymerase chain reaction(RT-PCR).The action of phosphorylation of p38MAPK was determined by Western blotting.RESULTS:Astragaloside raised the survival rates of mice with DCM,decreased LV dilation and dysfunction.Compared with controls,the exceptional deposition of collagens in DCM was suppressed by Astr.High expression of p38MAPK phosphorylation in DCM mice was decreased by Astr.CONCLUSION:Astr attenuating ventricular remodeling may be associated with the decreased action of phosphorylation of p38MAPK in CVB3-induced murine DCM.

Received 27 November 2008; revised 16 April 2009; accepted 21 April 2009. Available online 4 May 2009.

AbstractParkinson's disease (PD) is caused by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of Parkinson's disease. In the present study, Astragaloside IV (AS-IV) extracted from the dried root of Astragalus membranaceus, a well-known Chinese medicine used for the treatment of neurodegenerative diseases, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. By examining the effect of AS-IV on 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic neurons in primary nigral culture, we found that AS-IV pretreatment significantly and dose-dependently attenuated 6-OHDA-induced loss of dopaminergic neurons. Neuronal fiber length studies showed that massive neuronal cell death with degenerated neurons was observed in those cultures incubated with 6-OHDA, whereas in AS-IV co-treatments most dopaminergic neurons were seen to be intact and sprouting. In flow cytometric analysis, AS-IV resulted in a marked and dose-dependent rescue in tyrosine hydrolase (TH)-immunopositive cells from 6-OHDA-induced degeneration of dopaminergic neurons. Double immunofluorescence revealed that AS-IV treatment alone at concentrations of 100 and 200 μM increased the level of TH and NOS (nitrite oxide synthase) immunoreactivities; however, the protective effect of AS-IV on TH and NOS immunopositive cells in 6-OHDA treated nigral cell cultures was only seen at a concentration of 100 μM. These findings show that AS-IV can protect dopaminergic neurons against 6-OHDA-induced degeneration. Besides the neuroprotective effect, AS-IV alone promoted neurite outgrowth and increased TH and NOS immunoreactive of dopaminergic neurons. The neuroprotective and neurosprouting effects of AS-IV are specific for dopaminergic neurons and it has therapeutic potential in the treatment of PD.

Received 29 December 2003; Revised 23 February 2004; accepted 15 March 2004. Available online 2 June 2004.

AbstractAstragalus membranaceus is a herbal medicine that has been used clinically in stroke patients in China for decades, but its potential neuroprotective effect against ischemic brain injury has not been experimentally tested. In this study, we investigated the effect of Astragaloside IV, a purified extract from Astragalus membranaceus, in a murine model of focal cerebral ischemia/reperfusion produced by transient (1.5 h) middle cerebral artery occlusion. As determined at 72 h after ischemia, post-ischemic treatment of Astragaloside IV (20 or 40 mg/kg) markedly and significantly (P<0.03 vs. vehicle-treated animals) reduced infarct volume. Astragaloside IV treatment also decreased the levels of malondialdehyde, an indicator of lipid peroxidation, and increased the levels of the antioxidant enzymes glutathione peroxidase and superoxide dismutase in ischemic tissues. The results presented here provide the first evidence of a neuroprotective effect of Astragaloside IV in the model of ischemic brain injury. We suggest that the anti-infarction effect by Astragaloside IV may be derived at least in part from its antioxidant properties.

BACKGROUND: Repairing wound by using stem cells technology is an important strategy in the wound healing treatment of current medical field. Radix Astragalis, which strengthening body resistance, benefiting vital energy, promoting blood flow and anti-aging, has been widely applied in the treatment of many clinical diseases and syndromes. OBJECTIVE: To investigate the regulatory effect of Radix Astragalis on the proliferation of human epidermal stem cells derived from human skin. DESIGN, TIME AND SETTING: The cell, molecular biology experiment was performed at the First Affiliated Hospital, Nanchang University from September 2005 to June 2008. MATERIALS: Remaining free skin graft of burn and plastic patients was obtained from Burn Center, First Affiliated Hospital, Nanchang University. Radix Astragalis injection solution was purchased from Zhengda Qingchunbao, China (lot number 0207114), astragaloside .1.0mg per milliliter, equal to 2 g crude drug. METHODS: Epidermis was dissociated by Trypsin-ethylenediamine tetraacetic acid (EDTA). The type IV collagen was used to isolate and purify the human epidermal stem cells. The cultured cells in experimental group were treated with keratinocyte serum-free medium (KSFM) supplemented with Radix Astragalis and epidermal growth factor in vitro. The procedures were identical in control group, but no Radix Astragalis were added. MAIN OUTCOME MEASURES: The colony forming efficiency was calculated. The cell cycle was determined by the flow cytometer. The expression of the telomerase reverse transcriptase in epidermal stem cells was detected by the immunocytochemistry staining and the image quantitative analysis. RESULTS: Epidermal stem cells presented adhered to the wall, and large cell clone formed at 10 days. The colony forming efficiency of the epidermal stem cells in experimental group and the proportion of the epidermal stem cell in G(0)/G(1) period were significantly higher than in control group (t=3.17, P < 0.01; t =2.83, P < 0.05). The telomerase reverse transcriptase had positive expression in the epidermal stem cells of both groups. The average value of absorbance and positive area in experimental group was much higher than in control group (t=2.25, P < 0.05; t =4.12, P < 0.01). CONCLUSION: Radix Astragalis can effectively increase the cellular expression of telomerase reverse transcriptase and the proliferative activities of human epidermal stem cells derived from human skin in vitro.

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